FLT3: receptor and ligand

FLT3 is a receptor tyrosine kinase (RTK) expressed by immature hematopoietic progenitor cells. The ligand for FLT3 is a transmembrane or soluble protein and is expressed by a variety of cells including hematopoietic and marrow stromal cells; in combination with other growth factors, the ligand stimulates proliferation and development of stem cells, myeloid and lymphoid progenitor cells, dendritic cells and natural killer cells. Activation of the receptor leads to tyrosine phosphorylation of various key adaptor proteins known to be involved in different signal transduction pathways that control proliferation, survival and other processes in hematopoietic cells. FLT3 is not only of utmost interest regarding physiological processes of hematopoietic cells but also with regard to pathological aspects, namely leukemogenesis and diagnosis, prognosis and therapy of leukemia. Activating mutations of the receptor have been recognized as the most common genetic abnormality in acute myeloid leukemia (AML), occurring in about 30% of adult cases. AML patients with FLT3 mutations tend to have a poor prognosis, thus FLT3 is an attractive target of therapy, for instance using kinase inhibitors.